TYRO_HUMAN
ID TYRO_HUMAN Reviewed; 529 AA.
AC P14679; Q15675; Q15676; Q15680; Q8TAK4; Q9BYY0; Q9BZX1;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 3.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Tyrosinase;
DE EC=1.14.18.1;
DE AltName: Full=LB24-AB;
DE AltName: Full=Monophenol monooxygenase;
DE AltName: Full=SK29-AB;
DE AltName: Full=Tumor rejection antigen AB;
DE Flags: Precursor;
GN Name=TYR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=1903356; DOI=10.1016/0888-7543(91)90409-8;
RA Giebel L.B., Strunk K.M., Spritz R.A.;
RT "Organization and nucleotide sequences of the human tyrosinase gene and a
RT truncated tyrosinase-related segment.";
RL Genomics 9:435-445(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2823263; DOI=10.1073/pnas.84.21.7473;
RA Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R.;
RT "Isolation and sequence of a cDNA clone for human tyrosinase that maps at
RT the mouse c-albino locus.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7473-7477(1987).
RN [3]
RP ERRATUM OF PUBMED:2823263, AND SEQUENCE REVISION TO 384-398.
RA Kwon B.S., Haq A.K., Pomerantz S.H., Halaban R.;
RL Proc. Natl. Acad. Sci. U.S.A. 85:6352-6352(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Melanoma;
RX PubMed=2499655; DOI=10.1084/jem.169.6.2029;
RA Bouchard B., Fuller B.B., Vijayasaradhi S., Houghton A.N.;
RT "Induction of pigmentation in mouse fibroblasts by expression of human
RT tyrosinase cDNA.";
RL J. Exp. Med. 169:2029-2042(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1711223; DOI=10.1073/pnas.88.12.5272;
RA Chintamaneni C.D., Halaban R., Kobayashi Y., Witkop C.J., Kwon B.S.;
RT "A single base insertion in the putative transmembrane domain of the
RT tyrosinase gene as a cause for tyrosinase-negative oculocutaneous
RT albinism.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5272-5276(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RC TISSUE=Melanoma, and T-cell;
RX PubMed=8340755; DOI=10.1084/jem.178.2.489;
RA Brichard V., van Pel A., Woelfel T., Woelfel C., de Plaen E., Lethe B.G.,
RA Coulie P., Boon T.;
RT "The tyrosinase gene codes for an antigen recognized by autologous
RT cytolytic T lymphocytes on HLA-A2 melanomas.";
RL J. Exp. Med. 178:489-495(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT TYR-192.
RX PubMed=11153699; DOI=10.1034/j.1600-0749.2000.130609.x;
RA Martinez-Arias R., Comas D., Andres A., Abello M.-T., Domingo-Roura X.,
RA Bertranpetit J.;
RT "The tyrosinase gene in gorillas and the albinism of 'Snowflake'.";
RL Pigment Cell Res. 13:467-470(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-272.
RC TISSUE=Liver;
RX PubMed=2480811; DOI=10.1016/0167-4781(89)90115-2;
RA Kikuchi H., Miura H., Yamamoto H., Takeuchi T., Dei T., Watanabe M.;
RT "Characteristic sequences in the upstream region of the human tyrosinase
RT gene.";
RL Biochim. Biophys. Acta 1009:283-286(1989).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-32.
RX PubMed=2504160; DOI=10.1016/0006-291x(89)90770-5;
RA Takeda A., Tomita Y., Okinaga S., Tagami H., Shibahara S.;
RT "Functional analysis of the cDNA encoding human tyrosinase precursor.";
RL Biochem. Biophys. Res. Commun. 162:984-990(1989).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 54-195, AND VARIANT TYR-192.
RX PubMed=11214319; DOI=10.1038/35054550;
RA Murphy W.J., Eizirik E., Johnson W.E., Zhang Y.-P., Ryder O.A.,
RA O'Brien S.J.;
RT "Molecular phylogenetics and the origins of placental mammals.";
RL Nature 409:614-618(2001).
RN [12]
RP REVIEW ON OCA VARIANTS.
RX PubMed=8477259; DOI=10.1002/humu.1380020102;
RA Oetting W.S., King R.A.;
RT "Molecular basis of type I (tyrosinase-related) oculocutaneous albinism:
RT mutations and polymorphisms of the human tyrosinase gene.";
RL Hum. Mutat. 2:1-6(1993).
RN [13]
RP REVIEW ON OCA1 VARIANTS.
RX PubMed=10094567;
RX DOI=10.1002/(sici)1098-1004(1999)13:2<99::aid-humu2>3.0.co;2-c;
RA Oetting W.S., King R.A.;
RT "Molecular basis of albinism: mutations and polymorphisms of pigmentation
RT genes associated with albinism.";
RL Hum. Mutat. 13:99-115(1999).
RN [14]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J.,
RA Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F.,
RA Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [15]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [16]
RP INTERACTION WITH DCT.
RX PubMed=28842328; DOI=10.1016/j.jid.2017.07.833;
RA Regazzetti C., Sormani L., Debayle D., Bernerd F., Tulic M.K.,
RA De Donatis G.M., Chignon-Sicard B., Rocchi S., Passeron T.;
RT "Melanocytes Sense Blue Light and Regulate Pigmentation through Opsin-3.";
RL J. Invest. Dermatol. 138:171-178(2018).
RN [17]
RP VARIANTS OCA1A LYS-373 AND ASN-383, AND VARIANTS TYR-192 AND GLN-402.
RX PubMed=2342539; DOI=10.1056/nejm199006143222407;
RA Spritz R.A., Strunk K.M., Giebel L.B., King R.A.;
RT "Detection of mutations in the tyrosinase gene in a patient with type IA
RT oculocutaneous albinism.";
RL N. Engl. J. Med. 322:1724-1728(1990).
RN [18]
RP VARIANT OCA1A LEU-81.
RX PubMed=1970634; DOI=10.1073/pnas.87.9.3255;
RA Giebel L.B., Strunk K.M., King R.A., Hanifin J.M., Spritz R.A.;
RT "A frequent tyrosinase gene mutation in classic, tyrosinase-negative (type
RT IA) oculocutaneous albinism.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:3255-3258(1990).
RN [19]
RP VARIANTS OCA1B PHE-275 AND LEU-406.
RX PubMed=1903591;
RA Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E.,
RA King R.A., Spritz R.A.;
RT "Tyrosinase gene mutations associated with type IB ('yellow')
RT oculocutaneous albinism.";
RL Am. J. Hum. Genet. 48:1159-1167(1991).
RN [20]
RP ERRATUM OF PUBMED:1903591.
RA Giebel L.B., Tripathi R.K., Strunk K.M., Hanifin J.M., Jackson C.E.,
RA King R.A., Spritz R.A.;
RL Am. J. Hum. Genet. 49:696-696(1991).
RN [21]
RP VARIANTS OCA1A SER-21; TRP-217; HIS-299; SER-403; SER-446 AND ASN-448.
RX PubMed=1642278; DOI=10.1002/ajmg.1320430523;
RA Tripathi R.K., Strunk K.M., Giebel L.B., Weleber R.G., Spritz R.A.;
RT "Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous
RT albinism define two clusters of missense substitutions.";
RL Am. J. Med. Genet. 43:865-871(1992).
RN [22]
RP VARIANT OCA1A ARG-89.
RX PubMed=1899321;
RA Spritz R.A., Strunk K.M., Hsieh C.-L., Sekhon G.S., Francke U.;
RT "Homozygous tyrosinase gene mutation in an American black with tyrosinase-
RT negative (type IA) oculocutaneous albinism.";
RL Am. J. Hum. Genet. 48:318-324(1991).
RN [23]
RP VARIANT OCA1B GLN-422.
RX PubMed=1900309; DOI=10.1172/jci115075;
RA Giebel L.B., Tripathi R.K., King R.A., Spritz R.A.;
RT "A tyrosinase gene missense mutation in temperature-sensitive type I
RT oculocutaneous albinism. A human homologue to the Siamese cat and the
RT Himalayan mouse.";
RL J. Clin. Invest. 87:1119-1122(1991).
RN [24]
RP VARIANTS OCA1A GLY-42; TYR-55; THR-206 AND ARG-419.
RX PubMed=1943686;
RA King R.A., Mentink M.M., Oetting W.S.;
RT "Non-random distribution of missense mutations within the human tyrosinase
RT gene in type I (tyrosinase-related) oculocutaneous albinism.";
RL Mol. Biol. Med. 8:19-29(1991).
RN [25]
RP VARIANTS OCA1A ILE-176 AND GLN-217.
RX PubMed=1487241; DOI=10.1007/bf00220074;
RA Oetting W.S., King R.A.;
RT "Molecular analysis of type I-A (tyrosinase negative) oculocutaneous
RT albinism.";
RL Hum. Genet. 90:258-262(1992).
RN [26]
RP VARIANTS OCA1A GLN-328; ARG-419 AND LEU-431.
RX PubMed=7902671;
RA Tripathi R.K., Bundey S., Musarella M.A., Droetto S., Strunk K.M.,
RA Holmes S.A., Spritz R.A.;
RT "Mutations of the tyrosinase gene in Indo-Pakistani patients with type I
RT (tyrosinase-deficient) oculocutaneous albinism (OCA).";
RL Am. J. Hum. Genet. 53:1173-1179(1993).
RN [27]
RP VARIANTS OCA1A ASP-47; CYS-217 DEL; HIS-299 AND LYS-373, AND VARIANTS OCA1B
RP SER-152 AND LYS-294.
RX PubMed=8128955;
RA Gershoni-Baruch R., Rosenmann A., Droetto S., Holmes S.A., Tripathi R.K.,
RA Spritz R.A.;
RT "Mutations of the tyrosinase gene in patients with oculocutaneous albinism
RT from various ethnic groups in Israel.";
RL Am. J. Hum. Genet. 54:586-594(1994).
RN [28]
RP VARIANTS OCA1A TYR-367; THR-370 AND LYS-373, AND VARIANT GLN-402.
RX PubMed=7955413; DOI=10.1016/0009-8981(94)90131-7;
RA Breimer L.H., Winder A.F., Jay B., Jay M.;
RT "Initiation codon mutation of the tyrosinase gene as a cause of human
RT albinism.";
RL Clin. Chim. Acta 227:17-22(1994).
RN [29]
RP VARIANTS OCA1A ARG-361 AND TYR-371.
RX PubMed=8644824; DOI=10.1016/s0002-9394(14)70647-6;
RA Summers C.G., Oetting W.S., King R.A.;
RT "Diagnosis of oculocutaneous albinism with molecular analysis.";
RL Am. J. Ophthalmol. 121:724-726(1996).
RN [30]
RP VARIANT GLN-402.
RX PubMed=9158138; DOI=10.1093/hmg/6.5.659;
RA Morell R., Spritz R.A., Ho L., Pierpont J., Guo W., Friedman T.B.,
RA Asher J.H. Jr.;
RT "Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and
RT autosomal recessive ocular albinism (AROA).";
RL Hum. Mol. Genet. 6:659-664(1997).
RN [31]
RP VARIANTS OCA1A AND OCA1B.
RX PubMed=9259202;
RX DOI=10.1002/(sici)1098-1004(1997)10:2<171::aid-humu11>3.0.co;2-x;
RA Spritz R.A., Oh J., Fukai K., Holmes S.A., Ho L., Chitayat D., France T.D.,
RA Musarella M.A., Orlow S.J., Schnur R.E., Weleber R.G., Levin A.V.;
RT "Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous
RT albinism (OCA1).";
RL Hum. Mutat. 10:171-174(1997).
RN [32]
RP VARIANTS OCA1A AND OCA1B.
RX PubMed=10671066;
RX DOI=10.1002/(sici)1098-1004(1998)12:6<433::aid-humu14>3.0.co;2-g;
RA Oetting W.S., Fryer J.P., King R.A.;
RT "Mutations of the human tyrosinase gene associated with tyrosinase related
RT oculocutaneous albinism (OCA1).";
RL Hum. Mutat. 12:433-434(1998).
RN [33]
RP ERRATUM OF PUBMED:10671066.
RA Oetting W.S., Fryer J.P., King R.A.;
RL Hum. Mutat. 13:83-83(1999).
RN [34]
RP VARIANTS OCA1A TYR-36; GLN-77; TRP-77; LEU-81; ARG-97; GLN-217; TRP-217;
RP SER-236; CYS-272; ARG-289; GLY-294; LYS-294; PRO-355; TYR-371; LYS-373;
RP LEU-406; ARG-419; GLN-422; VAL-439; SER-446 AND ASN-448, VARIANT OCA1B
RP SER-403, AND VARIANTS TYR-192 AND GLN-402.
RX PubMed=10987646; DOI=10.1007/s004390051090;
RA Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.;
RT "Novel and recurrent mutations in the tyrosinase gene and the P gene in the
RT German albino population.";
RL Hum. Genet. 105:200-210(1999).
RN [35]
RP ERRATUM OF PUBMED:10987646.
RA Passmore L.A., Kaesmann-Kellner B., Weber B.H.F.;
RL Hum. Genet. 108:208-208(2001).
RN [36]
RP VARIANTS OCA1A TYR-55; ARG-77 INS; GLY-289; HIS-299; SER-299 AND LEU-400.
RX PubMed=10571953;
RX DOI=10.1002/(sici)1098-1004(199912)14:6<542::aid-humu14>3.0.co;2-3;
RA Tsai C.-H., Tsai F.-J., Wu J.-Y., Lin S.-P., Chang J.-G., Yang C.-F.,
RA Lee C.-C.;
RT "Insertion/deletion mutations of type I oculocutaneous albinism in Chinese
RT patients from Taiwan.";
RL Hum. Mutat. 14:542-542(1999).
RN [37]
RP VARIANTS OCA1A ASP-47; GLN-77; ARG-109; THR-205; TYR-256; PHE-275; LYS-294;
RP GLY-339; PRO-355; LYS-373; ASN-383 AND SER-446.
RX PubMed=11295837; DOI=10.1002/humu.38;
RA Camand O., Marchant D., Boutboul S., Pequignot M., Odent S., Dollfus H.,
RA Sutherland J., Levin A., Menasche M., Marsac C., Dufier J.-L., Heon E.,
RA Abitbol M.;
RT "Mutation analysis of the tyrosinase gene in oculocutaneous albinism.";
RL Hum. Mutat. 17:352-352(2001).
RN [38]
RP VARIANT OCA1A TRP-239.
RX PubMed=11858948; DOI=10.1016/s0923-1811(01)00141-4;
RA Nakamura E., Miyamura Y., Matsunaga J., Kano Y., Dakeishi-Hara M.,
RA Tanita M., Kono M., Tomita Y.;
RT "A novel mutation of the tyrosinase gene causing oculocutaneous albinism
RT type 1 (OCA1).";
RL J. Dermatol. Sci. 28:102-105(2002).
RN [39]
RP VARIANTS OCA1A ARG-44; GLY-44; ASP-47; VAL-47; HIS-68; GLN-77; LEU-79;
RP LEU-81; SER-155; PHE-177; LEU-179; ASN-180; ASN-199; SER-201; SER-217;
RP LEU-236; VAL-240; THR-243; TYR-256; ARG-289; GLU-318; PRO-329; THR-332;
RP GLY-345; PRO-355; LYS-373; LYS-378; ASN-383; PHE-393; ARG-395; VAL-398;
RP ALA-398; LEU-402; SER-403; ASN-404; LEU-405; LEU-406; HIS-408; ASP-409;
RP SER-416; HIS-417; ARG-419; GLN-422; PHE-424; LYS-426; GLY-427; ILE-434;
RP ASP-435; GLY-444 AND ASN-448, AND VARIANTS TYR-192 AND GLN-402.
RX PubMed=15146472; DOI=10.1002/humu.9248;
RA Opitz S., Kaesmann-Kellner B., Kaufmann M., Schwinger E., Zuehlke C.;
RT "Detection of 53 novel DNA variations within the tyrosinase gene and
RT accumulation of mutations in 17 patients with albinism.";
RL Hum. Mutat. 23:630-631(2004).
RN [40]
RP VARIANT TYR-192, AND ASSOCIATION WITH SHEP3.
RX PubMed=17999355; DOI=10.1086/522235;
RA Stokowski R.P., Pant P.V.K., Dadd T., Fereday A., Hinds D.A., Jarman C.,
RA Filsell W., Ginger R.S., Green M.R., van der Ouderaa F.J., Cox D.R.;
RT "A genomewide association study of skin pigmentation in a South Asian
RT population.";
RL Am. J. Hum. Genet. 81:1119-1132(2007).
RN [41]
RP VARIANT TYR-192, AND ASSOCIATION WITH SHEP3.
RX PubMed=17952075; DOI=10.1038/ng.2007.13;
RA Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T.,
RA Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G.,
RA Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B.,
RA Thorisdottir K., Ragnarsson R., Benediktsdottir K.R., Aben K.K.,
RA Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U.,
RA Stefansson K.;
RT "Genetic determinants of hair, eye and skin pigmentation in Europeans.";
RL Nat. Genet. 39:1443-1452(2007).
RN [42]
RP VARIANT OCA1A TYR-91.
RX PubMed=22981120; DOI=10.1016/j.ajhg.2012.08.007;
RA Chong J.X., Ouwenga R., Anderson R.L., Waggoner D.J., Ober C.;
RT "A population-based study of autosomal-recessive disease-causing mutations
RT in a founder population.";
RL Am. J. Hum. Genet. 91:608-620(2012).
RN [43]
RP VARIANTS OCA1A LEU-50; TRP-77; PHE-275; TRP-298; VAL-355; HIS-364; LYS-373;
RP ALA-384 AND ASP-490.
RX PubMed=23504663; DOI=10.1002/humu.22315;
RA Simeonov D.R., Wang X., Wang C., Sergeev Y., Dolinska M., Bower M.,
RA Fischer R., Winer D., Dubrovsky G., Balog J.Z., Huizing M., Hart R.,
RA Zein W.M., Gahl W.A., Brooks B.P., Adams D.R.;
RT "DNA variations in oculocutaneous albinism: an updated mutation list and
RT current outstanding issues in molecular diagnostics.";
RL Hum. Mutat. 34:827-835(2013).
RN [44]
RP VARIANT OCA1A THR-198.
RX PubMed=24934919; DOI=10.1111/ced.12382;
RA Shah S.A., Din S.U., Raheem N., Daud S., Mubeen J., Nadeem A., Tayyab M.,
RA Baloch D.M., Babar M.E., Ahmad J.;
RT "Identification of a novel mutation (p.Ile198Thr) in gene TYR in a
RT Pakistani family with nonsyndromic oculocutaneous albinism.";
RL Clin. Exp. Dermatol. 39:646-648(2014).
CC -!- FUNCTION: This is a copper-containing oxidase that functions in the
CC formation of pigments such as melanins and other polyphenolic compounds
CC (By similarity). Catalyzes the initial and rate limiting step in the
CC cascade of reactions leading to melanin production from tyrosine (By
CC similarity). In addition to hydroxylating tyrosine to DOPA (3,4-
CC dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-
CC quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to
CC indole-5,6 quinone (By similarity). {ECO:0000250|UniProtKB:P11344}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 L-dopa + O2 = 2 H2O + 2 L-dopaquinone; Xref=Rhea:RHEA:34287,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57504,
CC ChEBI:CHEBI:57924; EC=1.14.18.1;
CC Evidence={ECO:0000250|UniProtKB:P11344};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosine + O2 = H2O + L-dopaquinone; Xref=Rhea:RHEA:18117,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:57924,
CC ChEBI:CHEBI:58315; EC=1.14.18.1;
CC Evidence={ECO:0000250|UniProtKB:P11344};
CC -!- COFACTOR:
CC Name=Cu(2+); Xref=ChEBI:CHEBI:29036;
CC Evidence={ECO:0000250|UniProtKB:Q9ZP19};
CC Note=Binds 2 copper ions per subunit. {ECO:0000250|UniProtKB:Q9ZP19};
CC -!- SUBUNIT: Forms an OPN3-dependent complex with DCT in response to blue
CC light in melanocytes. {ECO:0000269|PubMed:28842328}.
CC -!- INTERACTION:
CC P14679; P51810: GPR143; NbExp=4; IntAct=EBI-25397340, EBI-2509708;
CC P14679-2; Q14457: BECN1; NbExp=3; IntAct=EBI-25894402, EBI-949378;
CC P14679-2; P26641: EEF1G; NbExp=3; IntAct=EBI-25894402, EBI-351467;
CC P14679-2; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-25894402, EBI-17438286;
CC P14679-2; Q6ZMY6-2: WDR88; NbExp=3; IntAct=EBI-25894402, EBI-25857007;
CC -!- SUBCELLULAR LOCATION: Melanosome membrane {ECO:0000269|PubMed:12643545,
CC ECO:0000269|PubMed:17081065}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:12643545, ECO:0000269|PubMed:17081065}. Melanosome
CC {ECO:0000250|UniProtKB:P11344}. Note=Proper trafficking to melanosome
CC is regulated by SGSM2, ANKRD27, RAB9A, RAB32 and RAB38.
CC {ECO:0000250|UniProtKB:P11344}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P14679-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P14679-2; Sequence=VSP_006701, VSP_006702;
CC -!- INDUCTION: Increased expression after UVB irradiation.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P11344}.
CC -!- POLYMORPHISM: Genetic variants in TYR define the skin/hair/eye
CC pigmentation variation locus 3 (SHEP3) [MIM:601800]. Hair, eye and skin
CC pigmentation are among the most visible examples of human phenotypic
CC variation, with a broad normal range that is subject to substantial
CC geographic stratification. In the case of skin, individuals tend to
CC have lighter pigmentation with increasing distance from the equator. By
CC contrast, the majority of variation in human eye and hair color is
CC found among individuals of European ancestry, with most other human
CC populations fixed for brown eyes and black hair.
CC {ECO:0000269|PubMed:17952075, ECO:0000269|PubMed:17999355}.
CC -!- POLYMORPHISM: Compound heterozygosity for the R402Q polymorphism and a
CC mutant allele of TYR is a common cause of autosomal recessive ocular
CC albinism. The R402Q polymorphism is also found in Waardenburg syndrome
CC type II with ocular albinism in association with a deletion in the MITF
CC gene. {ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:7955413,
CC ECO:0000269|PubMed:9158138}.
CC -!- DISEASE: Albinism, oculocutaneous, 1A (OCA1A) [MIM:203100]: An
CC autosomal recessive disorder in which the biosynthesis of melanin
CC pigment is absent in skin, hair, and eyes. It is characterized by
CC complete lack of tyrosinase activity due to production of an inactive
CC enzyme. Patients present with a life-long absence of melanin pigment
CC after birth, and manifest increased sensitivity to ultraviolet
CC radiation with predisposition to skin cancer. Visual anomalies include
CC decreased acuity, nystagmus, strabismus and photophobia.
CC {ECO:0000269|PubMed:10571953, ECO:0000269|PubMed:10671066,
CC ECO:0000269|PubMed:10987646, ECO:0000269|PubMed:11295837,
CC ECO:0000269|PubMed:11858948, ECO:0000269|PubMed:1487241,
CC ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278,
CC ECO:0000269|PubMed:1899321, ECO:0000269|PubMed:1943686,
CC ECO:0000269|PubMed:1970634, ECO:0000269|PubMed:22981120,
CC ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:23504663,
CC ECO:0000269|PubMed:24934919, ECO:0000269|PubMed:7902671,
CC ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:8128955,
CC ECO:0000269|PubMed:8644824, ECO:0000269|PubMed:9259202}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Albinism, oculocutaneous, 1B (OCA1B) [MIM:606952]: An
CC autosomal recessive disorder in which the biosynthesis of melanin
CC pigment is reduced in skin, hair, and eyes. It is characterized by
CC partial lack of tyrosinase activity. Patients have white hair at birth
CC that rapidly turns yellow or blond. They manifest the development of
CC minimal-to-moderate amounts of cutaneous and ocular pigment. Some
CC patients may have with white hair in the warmer areas (scalp and
CC axilla) and progressively darker hair in the cooler areas
CC (extremities). This variant phenotype is due to a loss of tyrosinase
CC activity above 35-37 degrees C. {ECO:0000269|PubMed:10987646,
CC ECO:0000269|PubMed:1900309, ECO:0000269|PubMed:1903591,
CC ECO:0000269|PubMed:8128955}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tyrosinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA61241.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA68756.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mutations of the TYR gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/tyrmut.htm";
CC -!- WEB RESOURCE: Name=Albinism database (ADB); Note=TYR mutations;
CC URL="http://www.ifpcs.org/albinism/oca1mut.html";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Snowy stardom - Issue 49 of
CC August 2004;
CC URL="https://web.expasy.org/spotlight/back_issues/049";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tyrosinase entry;
CC URL="https://en.wikipedia.org/wiki/Tyrosinase";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TYRID42738ch11q14.html";
CC ---------------------------------------------------------------------------
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DR EMBL; M27160; AAB37227.1; -; mRNA.
DR EMBL; M63239; AAA61242.1; -; Genomic_DNA.
DR EMBL; M63235; AAA61242.1; JOINED; Genomic_DNA.
DR EMBL; M63236; AAA61242.1; JOINED; Genomic_DNA.
DR EMBL; M63237; AAA61242.1; JOINED; Genomic_DNA.
DR EMBL; M63238; AAA61242.1; JOINED; Genomic_DNA.
DR EMBL; J03581; AAA61241.1; ALT_INIT; mRNA.
DR EMBL; Y00819; CAA68756.1; ALT_INIT; mRNA.
DR EMBL; U01873; AAB60319.1; ALT_SEQ; mRNA.
DR EMBL; M74314; AAA61244.1; -; mRNA.
DR EMBL; X16073; CAA34205.1; -; Genomic_DNA.
DR EMBL; AF237811; AAK00805.1; -; Genomic_DNA.
DR EMBL; AF237807; AAK00805.1; JOINED; Genomic_DNA.
DR EMBL; AF237808; AAK00805.1; JOINED; Genomic_DNA.
DR EMBL; AF237809; AAK00805.1; JOINED; Genomic_DNA.
DR EMBL; AF237810; AAK00805.1; JOINED; Genomic_DNA.
DR EMBL; BC027179; AAH27179.1; -; mRNA.
DR EMBL; AY012019; AAG38762.1; -; Genomic_DNA.
DR CCDS; CCDS8284.1; -. [P14679-1]
DR PIR; A38444; YRHU1.
DR RefSeq; NP_000363.1; NM_000372.4. [P14679-1]
DR AlphaFoldDB; P14679; -.
DR SMR; P14679; -.
DR BioGRID; 113150; 4.
DR IntAct; P14679; 5.
DR STRING; 9606.ENSP00000263321; -.
DR BindingDB; P14679; -.
DR ChEMBL; CHEMBL1973; -.
DR DrugBank; DB11217; Arbutin.
DR DrugBank; DB00548; Azelaic acid.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB11254; Hexylresorcinol.
DR DrugBank; DB09526; Hydroquinone.
DR DrugBank; DB01055; Mimosine.
DR DrugBank; DB00600; Monobenzone.
DR DrugBank; DB00157; NADH.
DR DrugCentral; P14679; -.
DR TCDB; 9.B.423.1.1; the tysrosinase (tyr) family.
DR GlyGen; P14679; 6 sites.
DR iPTMnet; P14679; -.
DR PhosphoSitePlus; P14679; -.
DR BioMuta; TYR; -.
DR DMDM; 401235; -.
DR MassIVE; P14679; -.
DR PaxDb; P14679; -.
DR PeptideAtlas; P14679; -.
DR PRIDE; P14679; -.
DR ProteomicsDB; 53077; -. [P14679-1]
DR ProteomicsDB; 53078; -. [P14679-2]
DR ABCD; P14679; 3 sequenced antibodies.
DR Antibodypedia; 3663; 881 antibodies from 38 providers.
DR DNASU; 7299; -.
DR Ensembl; ENST00000263321.6; ENSP00000263321.4; ENSG00000077498.9. [P14679-1]
DR GeneID; 7299; -.
DR KEGG; hsa:7299; -.
DR MANE-Select; ENST00000263321.6; ENSP00000263321.4; NM_000372.5; NP_000363.1.
DR UCSC; uc001pcs.4; human. [P14679-1]
DR CTD; 7299; -.
DR DisGeNET; 7299; -.
DR GeneCards; TYR; -.
DR HGNC; HGNC:12442; TYR.
DR HPA; ENSG00000077498; Tissue enriched (skin).
DR MalaCards; TYR; -.
DR MIM; 203100; phenotype.
DR MIM; 601800; phenotype.
DR MIM; 606933; gene.
DR MIM; 606952; phenotype.
DR neXtProt; NX_P14679; -.
DR OpenTargets; ENSG00000077498; -.
DR Orphanet; 352734; Minimal pigment oculocutaneous albinism type 1.
DR Orphanet; 79431; Oculocutaneous albinism type 1A.
DR Orphanet; 79434; Oculocutaneous albinism type 1B.
DR Orphanet; 352737; Temperature-sensitive oculocutaneous albinism type 1.
DR Orphanet; 895; Waardenburg syndrome type 2.
DR PharmGKB; PA37095; -.
DR VEuPathDB; HostDB:ENSG00000077498; -.
DR eggNOG; ENOG502QRET; Eukaryota.
DR GeneTree; ENSGT00940000155336; -.
DR HOGENOM; CLU_038693_1_0_1; -.
DR InParanoid; P14679; -.
DR OMA; HWAPAFS; -.
DR PhylomeDB; P14679; -.
DR TreeFam; TF315865; -.
DR BioCyc; MetaCyc:HS01248-MON; -.
DR BRENDA; 1.14.18.1; 2681.
DR PathwayCommons; P14679; -.
DR Reactome; R-HSA-5662702; Melanin biosynthesis.
DR SABIO-RK; P14679; -.
DR SignaLink; P14679; -.
DR SIGNOR; P14679; -.
DR BioGRID-ORCS; 7299; 9 hits in 1066 CRISPR screens.
DR ChiTaRS; TYR; human.
DR GeneWiki; Tyrosinase; -.
DR GenomeRNAi; 7299; -.
DR Pharos; P14679; Tclin.
DR PRO; PR:P14679; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P14679; protein.
DR Bgee; ENSG00000077498; Expressed in pigmented layer of retina and 43 other tissues.
DR ExpressionAtlas; P14679; baseline and differential.
DR Genevisible; P14679; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005798; C:Golgi-associated vesicle; TAS:ProtInc.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; TAS:UniProtKB.
DR GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005507; F:copper ion binding; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004503; F:tyrosinase activity; IDA:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0006726; P:eye pigment biosynthetic process; TAS:ProtInc.
DR GO; GO:0042438; P:melanin biosynthetic process; IDA:CACAO.
DR GO; GO:0006583; P:melanin biosynthetic process from tyrosine; TAS:ProtInc.
DR GO; GO:0043473; P:pigmentation; IBA:GO_Central.
DR GO; GO:0009637; P:response to blue light; IDA:UniProtKB.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0009411; P:response to UV; IEA:Ensembl.
DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 1.10.1280.10; -; 1.
DR InterPro; IPR008922; Di-copper_centre_dom_sf.
DR InterPro; IPR002227; Tyrosinase_Cu-bd.
DR Pfam; PF00264; Tyrosinase; 1.
DR PRINTS; PR00092; TYROSINASE.
DR SUPFAM; SSF48056; SSF48056; 1.
DR PROSITE; PS00497; TYROSINASE_1; 1.
DR PROSITE; PS00498; TYROSINASE_2; 1.
PE 1: Evidence at protein level;
KW Albinism; Alternative splicing; Copper; Deafness; Disease variant;
KW Glycoprotein; Melanin biosynthesis; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Tumor antigen; Waardenburg syndrome.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..529
FT /note="Tyrosinase"
FT /id="PRO_0000035879"
FT TOPO_DOM 19..476
FT /note="Lumenal, melanosome"
FT /evidence="ECO:0000255"
FT TRANSMEM 477..497
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 498..529
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 287..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 180
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 202
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 211
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="A"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 363
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 367
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT BINDING 390
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="B"
FT /evidence="ECO:0000250|UniProtKB:Q9ZP19"
FT CARBOHYD 86
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 346..377
FT /note="GFASPLTGIADASQSSMHNALHIYMNGTMSQV -> EMGFLHVGWAGLKLLT
FT SRDPPPWPPKMLGLQA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_006701"
FT VAR_SEQ 378..529
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_006702"
FT VARIANT 19
FT /note="H -> Q (in OCA1A; dbSNP:rs61753177)"
FT /id="VAR_007649"
FT VARIANT 21
FT /note="P -> S (in OCA1A; dbSNP:rs61753178)"
FT /evidence="ECO:0000269|PubMed:1642278"
FT /id="VAR_007650"
FT VARIANT 36
FT /note="C -> Y (in OCA1A; dbSNP:rs61753179)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_021683"
FT VARIANT 42
FT /note="D -> G (in OCA1A; dbSNP:rs28940878)"
FT /evidence="ECO:0000269|PubMed:1943686"
FT /id="VAR_007651"
FT VARIANT 44
FT /note="S -> G (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021684"
FT VARIANT 44
FT /note="S -> R (in OCA1A; dbSNP:rs755700581)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021685"
FT VARIANT 47
FT /note="G -> D (in OCA1A; dbSNP:rs61753180)"
FT /evidence="ECO:0000269|PubMed:11295837,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:8128955"
FT /id="VAR_007652"
FT VARIANT 47
FT /note="G -> V (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021686"
FT VARIANT 50
FT /note="S -> L (in OCA1A; dbSNP:rs61753181)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072592"
FT VARIANT 52
FT /note="R -> I (in OCA1; dbSNP:rs61753182)"
FT /id="VAR_007653"
FT VARIANT 55
FT /note="C -> Y (in OCA1A; dbSNP:rs28940879)"
FT /evidence="ECO:0000269|PubMed:10571953,
FT ECO:0000269|PubMed:1943686"
FT /id="VAR_007654"
FT VARIANT 68
FT /note="Q -> H (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021687"
FT VARIANT 77
FT /note="R -> Q (in OCA1A; dbSNP:rs61753185)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:15146472"
FT /id="VAR_007655"
FT VARIANT 77
FT /note="R -> RR (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:10571953"
FT /id="VAR_009236"
FT VARIANT 77
FT /note="R -> W (in OCA1A; dbSNP:rs61753184)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:23504663"
FT /id="VAR_007656"
FT VARIANT 79
FT /note="S -> L (in OCA1A; dbSNP:rs544053015)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021688"
FT VARIANT 80
FT /note="W -> R (in OCA1A; dbSNP:rs61753188)"
FT /id="VAR_007657"
FT VARIANT 81
FT /note="P -> L (in OCA1A; dbSNP:rs28940876)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1970634"
FT /id="VAR_007658"
FT VARIANT 89
FT /note="C -> R (in OCA1A; dbSNP:rs28940877)"
FT /evidence="ECO:0000269|PubMed:1899321"
FT /id="VAR_007659"
FT VARIANT 91
FT /note="C -> Y (in OCA1A; dbSNP:rs137854890)"
FT /evidence="ECO:0000269|PubMed:22981120"
FT /id="VAR_072593"
FT VARIANT 97
FT /note="G -> R (in OCA1A; dbSNP:rs61753252)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_007660"
FT VARIANT 109
FT /note="G -> R (in OCA1A; dbSNP:rs61753253)"
FT /evidence="ECO:0000269|PubMed:11295837"
FT /id="VAR_021689"
FT VARIANT 134
FT /note="F -> C (in dbSNP:rs33955261)"
FT /id="VAR_034576"
FT VARIANT 142
FT /note="K -> N (in dbSNP:rs11545463)"
FT /id="VAR_042665"
FT VARIANT 152
FT /note="P -> S (in OCA1B; dbSNP:rs145513733)"
FT /evidence="ECO:0000269|PubMed:8128955"
FT /id="VAR_007925"
FT VARIANT 155
FT /note="T -> S (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021690"
FT VARIANT 176
FT /note="F -> I (in OCA1A; dbSNP:rs61753259)"
FT /evidence="ECO:0000269|PubMed:1487241"
FT /id="VAR_007661"
FT VARIANT 177
FT /note="V -> F (in OCA1A; dbSNP:rs138487695)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021691"
FT VARIANT 179
FT /note="M -> L (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021692"
FT VARIANT 180
FT /note="H -> N (in OCA1A; dbSNP:rs779878377)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021693"
FT VARIANT 192
FT /note="S -> Y (associated with SHEP3; light/dark skin;
FT dbSNP:rs1042602)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:11153699, ECO:0000269|PubMed:11214319,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:17952075,
FT ECO:0000269|PubMed:17999355, ECO:0000269|PubMed:2342539"
FT /id="VAR_007662"
FT VARIANT 198
FT /note="I -> T (in OCA1A; dbSNP:rs750553908)"
FT /evidence="ECO:0000269|PubMed:24934919"
FT /id="VAR_071756"
FT VARIANT 199
FT /note="D -> N (in OCA1A; dbSNP:rs1338186937)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021694"
FT VARIANT 201
FT /note="A -> S (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021695"
FT VARIANT 205
FT /note="P -> T (in OCA1A; dbSNP:rs61754362)"
FT /evidence="ECO:0000269|PubMed:11295837"
FT /id="VAR_021696"
FT VARIANT 206
FT /note="A -> T (in OCA1A; dbSNP:rs28940880)"
FT /evidence="ECO:0000269|PubMed:1943686"
FT /id="VAR_007663"
FT VARIANT 216
FT /note="L -> M (in OCA1A; dbSNP:rs61754363)"
FT /id="VAR_007664"
FT VARIANT 217
FT /note="R -> G (in OCA1A; dbSNP:rs63159160)"
FT /id="VAR_007665"
FT VARIANT 217
FT /note="R -> Q (in OCA1A; dbSNP:rs61754365)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:1487241"
FT /id="VAR_007667"
FT VARIANT 217
FT /note="R -> S (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021697"
FT VARIANT 217
FT /note="R -> W (in OCA1A; dbSNP:rs63159160)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:1642278"
FT /id="VAR_007666"
FT VARIANT 217
FT /note="Missing (in OCA1A)"
FT /id="VAR_007926"
FT VARIANT 227
FT /note="Missing (in OCA1A)"
FT /id="VAR_021698"
FT VARIANT 236
FT /note="W -> L (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021699"
FT VARIANT 236
FT /note="W -> S (in OCA1A; dbSNP:rs61754367)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_021700"
FT VARIANT 239
FT /note="R -> W (in OCA1A; dbSNP:rs774670098)"
FT /evidence="ECO:0000269|PubMed:11858948"
FT /id="VAR_021701"
FT VARIANT 240
FT /note="D -> V (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021702"
FT VARIANT 243
FT /note="K -> T (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021703"
FT VARIANT 253
FT /note="G -> R (in OCA1A; dbSNP:rs61754369)"
FT /id="VAR_007668"
FT VARIANT 256
FT /note="H -> Y (in OCA1A; dbSNP:rs61754370)"
FT /evidence="ECO:0000269|PubMed:11295837,
FT ECO:0000269|PubMed:15146472"
FT /id="VAR_021704"
FT VARIANT 272
FT /note="W -> C (in OCA1A; dbSNP:rs62645902)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_021705"
FT VARIANT 275
FT /note="V -> F (in OCA1B and OCA1A; dbSNP:rs104894314)"
FT /evidence="ECO:0000269|PubMed:11295837,
FT ECO:0000269|PubMed:1903591, ECO:0000269|PubMed:23504663"
FT /id="VAR_007669"
FT VARIANT 288
FT /note="L -> S (in OCA1A; dbSNP:rs1463109821)"
FT /id="VAR_007927"
FT VARIANT 289
FT /note="C -> G (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:10571953"
FT /id="VAR_009237"
FT VARIANT 289
FT /note="C -> R (in OCA1A; dbSNP:rs1468041471)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472"
FT /id="VAR_007670"
FT VARIANT 294
FT /note="E -> G (in OCA1A; dbSNP:rs1565391875)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_021706"
FT VARIANT 294
FT /note="E -> K (in OCA1A and OCA1B; dbSNP:rs757754120)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:8128955"
FT /id="VAR_007928"
FT VARIANT 298
FT /note="R -> W (in OCA1A; dbSNP:rs200854796)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072594"
FT VARIANT 299
FT /note="R -> H (in OCA1A; dbSNP:rs61754375)"
FT /evidence="ECO:0000269|PubMed:10571953,
FT ECO:0000269|PubMed:1642278, ECO:0000269|PubMed:8128955"
FT /id="VAR_007671"
FT VARIANT 299
FT /note="R -> S (in OCA1A; dbSNP:rs61754374)"
FT /evidence="ECO:0000269|PubMed:10571953"
FT /id="VAR_007672"
FT VARIANT 308
FT /note="R -> T (in dbSNP:rs1042608)"
FT /id="VAR_011825"
FT VARIANT 312
FT /note="L -> V (in OCA1; dbSNP:rs61754377)"
FT /id="VAR_007673"
FT VARIANT 313
FT /note="P -> R (in OCA1; dbSNP:rs61754378)"
FT /id="VAR_007674"
FT VARIANT 318
FT /note="V -> E (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021707"
FT VARIANT 325
FT /note="T -> A (in OCA1B; dbSNP:rs61754379)"
FT /id="VAR_007675"
FT VARIANT 328
FT /note="E -> Q (in OCA1A; dbSNP:rs61754380)"
FT /evidence="ECO:0000269|PubMed:7902671"
FT /id="VAR_007929"
FT VARIANT 329
FT /note="S -> P (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021708"
FT VARIANT 332
FT /note="M -> T (in OCA1A; dbSNP:rs372534292)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021709"
FT VARIANT 339
FT /note="S -> G (in OCA1A; dbSNP:rs62645906)"
FT /evidence="ECO:0000269|PubMed:11295837"
FT /id="VAR_007676"
FT VARIANT 340
FT /note="F -> L (in OCA1; dbSNP:rs62645907)"
FT /id="VAR_007677"
FT VARIANT 345
FT /note="E -> G (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021710"
FT VARIANT 346
FT /note="G -> E (in OCA1A; dbSNP:rs773970123)"
FT /id="VAR_007930"
FT VARIANT 355
FT /note="A -> E (in OCA1A)"
FT /id="VAR_007931"
FT VARIANT 355
FT /note="A -> P (in OCA1A; dbSNP:rs62645908)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:15146472"
FT /id="VAR_007678"
FT VARIANT 355
FT /note="A -> V (in OCA1A; dbSNP:rs151206295)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072595"
FT VARIANT 361
FT /note="S -> R (in OCA1A; dbSNP:rs61754383)"
FT /evidence="ECO:0000269|PubMed:8644824"
FT /id="VAR_007932"
FT VARIANT 364
FT /note="N -> H (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072596"
FT VARIANT 367
FT /note="H -> Y (in OCA1A; dbSNP:rs776054795)"
FT /evidence="ECO:0000269|PubMed:7955413"
FT /id="VAR_007933"
FT VARIANT 370
FT /note="M -> T (in OCA1A; dbSNP:rs61754385)"
FT /evidence="ECO:0000269|PubMed:7955413"
FT /id="VAR_007934"
FT VARIANT 371
FT /note="N -> T (in OCA1A; dbSNP:rs61754387)"
FT /id="VAR_007679"
FT VARIANT 371
FT /note="N -> Y (in OCA1A; dbSNP:rs61754386)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:8644824"
FT /id="VAR_007935"
FT VARIANT 373
FT /note="T -> K (in OCA1A; dbSNP:rs61754388)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:15146472,
FT ECO:0000269|PubMed:2342539, ECO:0000269|PubMed:23504663,
FT ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:8128955"
FT /id="VAR_007680"
FT VARIANT 378
FT /note="Q -> K (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021711"
FT VARIANT 380
FT /note="S -> P (in OCA1B; dbSNP:rs61754391)"
FT /id="VAR_007681"
FT VARIANT 382
FT /note="N -> K (in OCA1A; dbSNP:rs104894315)"
FT /id="VAR_007682"
FT VARIANT 383
FT /note="D -> N (in OCA1A; dbSNP:rs121908011)"
FT /evidence="ECO:0000269|PubMed:11295837,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:2342539"
FT /id="VAR_007683"
FT VARIANT 384
FT /note="P -> A (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072597"
FT VARIANT 390
FT /note="H -> D (in OCA1B; dbSNP:rs62645914)"
FT /id="VAR_007684"
FT VARIANT 393
FT /note="V -> F (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_007936"
FT VARIANT 395
FT /note="S -> N (in OCA1A; dbSNP:rs752344007)"
FT /id="VAR_007685"
FT VARIANT 395
FT /note="S -> R (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021712"
FT VARIANT 398
FT /note="E -> A (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021713"
FT VARIANT 398
FT /note="E -> V (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021714"
FT VARIANT 400
FT /note="W -> L (in OCA1A; dbSNP:rs62645916)"
FT /evidence="ECO:0000269|PubMed:10571953"
FT /id="VAR_009238"
FT VARIANT 402
FT /note="R -> G (in OCA1B)"
FT /id="VAR_007937"
FT VARIANT 402
FT /note="R -> L (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021715"
FT VARIANT 402
FT /note="R -> Q (in dbSNP:rs1126809)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:2342539,
FT ECO:0000269|PubMed:7955413, ECO:0000269|PubMed:9158138"
FT /id="VAR_007686"
FT VARIANT 403
FT /note="R -> S (in OCA1A and OCA1B; dbSNP:rs104894316)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278"
FT /id="VAR_007687"
FT VARIANT 404
FT /note="H -> N (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021716"
FT VARIANT 404
FT /note="H -> P (in OCA-I; dbSNP:rs62645920)"
FT /id="VAR_007688"
FT VARIANT 405
FT /note="R -> L (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021717"
FT VARIANT 406
FT /note="P -> L (in OCA1A and OCA1B; dbSNP:rs104894313)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1903591"
FT /id="VAR_007689"
FT VARIANT 408
FT /note="Q -> H (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021718"
FT VARIANT 409
FT /note="E -> D (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021719"
FT VARIANT 416
FT /note="A -> S (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021720"
FT VARIANT 417
FT /note="P -> H (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021721"
FT VARIANT 419
FT /note="G -> R (in OCA1A; dbSNP:rs61754392)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1943686,
FT ECO:0000269|PubMed:7902671"
FT /id="VAR_007690"
FT VARIANT 422
FT /note="R -> Q (in OCA1A and OCA1B; temperature sensitive
FT variant; dbSNP:rs61754393)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1900309"
FT /id="VAR_007691"
FT VARIANT 424
FT /note="S -> F (in OCA1A; dbSNP:rs758747581)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021722"
FT VARIANT 426
FT /note="M -> K (in OCA1A; dbSNP:rs1362285246)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021723"
FT VARIANT 427
FT /note="V -> G (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021724"
FT VARIANT 431
FT /note="P -> L (in OCA1A; dbSNP:rs281865325)"
FT /evidence="ECO:0000269|PubMed:7902671"
FT /id="VAR_007938"
FT VARIANT 434
FT /note="R -> I (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021725"
FT VARIANT 435
FT /note="N -> D (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021726"
FT VARIANT 439
FT /note="F -> V (in OCA1A; dbSNP:rs281865327)"
FT /evidence="ECO:0000269|PubMed:10987646"
FT /id="VAR_021727"
FT VARIANT 444
FT /note="D -> G (in OCA1A)"
FT /evidence="ECO:0000269|PubMed:15146472"
FT /id="VAR_021728"
FT VARIANT 446
FT /note="G -> S (in OCA1A; dbSNP:rs104894317)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:11295837, ECO:0000269|PubMed:1642278"
FT /id="VAR_007692"
FT VARIANT 448
FT /note="D -> N (in OCA1A; dbSNP:rs104894318)"
FT /evidence="ECO:0000269|PubMed:10987646,
FT ECO:0000269|PubMed:15146472, ECO:0000269|PubMed:1642278"
FT /id="VAR_007693"
FT VARIANT 490
FT /note="A -> D (in OCA1A; dbSNP:rs1050708792)"
FT /evidence="ECO:0000269|PubMed:23504663"
FT /id="VAR_072598"
FT CONFLICT 42..45
FT /note="DRSP -> TGV (in Ref. 2; AAA61241)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="M -> I (in Ref. 4; CAA68756)"
FT /evidence="ECO:0000305"
FT CONFLICT 373..378
FT /note="TMSQVQ -> HVPGT (in Ref. 2; AAA61241)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="L -> P (in Ref. 2; AAA61241/AAA61244)"
FT /evidence="ECO:0000305"
FT CONFLICT 520..523
FT /note="DYHS -> GLPQ (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 525..528
FT /note="YQSH -> VSEPFIKGLGNRVGPKSPDLTLTQSNVQVPENICWYFL (in
FT Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 529 AA; 60393 MW; 67211A91608A59E1 CRC64;
MLLAVLYCLL WSFQTSAGHF PRACVSSKNL MEKECCPPWS GDRSPCGQLS GRGSCQNILL
SNAPLGPQFP FTGVDDRESW PSVFYNRTCQ CSGNFMGFNC GNCKFGFWGP NCTERRLLVR
RNIFDLSAPE KDKFFAYLTL AKHTISSDYV IPIGTYGQMK NGSTPMFNDI NIYDLFVWMH
YYVSMDALLG GSEIWRDIDF AHEAPAFLPW HRLFLLRWEQ EIQKLTGDEN FTIPYWDWRD
AEKCDICTDE YMGGQHPTNP NLLSPASFFS SWQIVCSRLE EYNSHQSLCN GTPEGPLRRN
PGNHDKSRTP RLPSSADVEF CLSLTQYESG SMDKAANFSF RNTLEGFASP LTGIADASQS
SMHNALHIYM NGTMSQVQGS ANDPIFLLHH AFVDSIFEQW LRRHRPLQEV YPEANAPIGH
NRESYMVPFI PLYRNGDFFI SSKDLGYDYS YLQDSDPDSF QDYIKSYLEQ ASRIWSWLLG
AAMVGAVLTA LLAGLVSLLC RHKRKQLPEE KQPLLMEKED YHSLYQSHL
